Analysis of Genomic Ancestry and Characterization of a New Variant in MPS Type VII

Abstract Background Mucopolysaccharidosis (MPS) type VII is a storage disorder of autosomal recessive origin caused by a deficiency in a lysosomal enzyme that results in accumulation of glycosaminoglycans and in secondary metabolic pathway problems. It has systemic symptomatology that mainly includes progressive skeletal dysplasia, cardiovascular manifestations, hepatosplenomegaly, coarse facies and many other manifestations, with cognitive decline in most cases. A significant proportion of patients may present fetal hydrops. Pathogenic variations frequent in specific ethnic groups explain the higher incidence in some groups due to founder effect and/or endogamy. In Brazil, the variant most commonly found is the p.Leu176Phe. This study aims to investigate GUSB expression of the patient with MPSVII with a new mutation (p.Leu292Pro). Also, it has been investigating the ancestry 5 patients with MPS VII from Brazil regarding the Amerindian, African and European contribution. Results Analyses allowed the identification of different proportions in the population contribution in the sample of patients with MPSVII with the highest European contribution which is significantly different (p = 0.0031) from the African contribution. Relative expression analysis by the 2 −ΔCT method that showed superior expression of the GUSB gene in the patient with MPSVII compared to the group without the disease. Relative the comparison among threshold cycles, 14/20 samples showed significantly different CT values for the patient with MPS VII when comparing the amplification cycles. The relatives also showed different values (p < 0.05) for the amplification cycles. The in silico prediction of the new variant indicated it as pathogenic by modifying a highly conserved region. Conclusions It has been indicated that the Leu176Phe mutation is possibly of European origin. There is a discrepancy between the levels of mRNA for GUSB and the amount of beta-glucuronidase synthesized. The p.Leu292Pro mutation is indicated as pathogenic, but its impact on the MPS VII phenotype still need to be fully elucidated.